Although it is known that human fetal membranes (amnion and chorion) contain renin, chorionic gonadotropin (HCG), prostaglandins and possibly other hormones, their regulation and function are unknown. Preliminary work in our laboratories indicates that renin inactive renin and HCG are present in term amnion and in trophoblast cells of the chorion laeve. We have also detected renin release from chorionic membranes and from cultured trophoblasts. The purpose of the proposed research is to gain an understanding of the cellular regulation of renin and other hormones in human fetal membranes in normal pregnancy and in certain pathological conditions. The techniques to be employed include (1) Superfusion of isolated membranes to study the effects of drugs, ions, nucleotides, and hormones on the release of renin, inactive renin, HCG, prostaglandins and steroid hormones. These studies will parallel studies in the P.I.'s laboratory on stimulus-secretion coupling and will examine factors known to influence the release of these substances from other tissues. (2) Studies on isolated chorionic cells both acutely and in tissue culture to examine renin and hormone regulation. Studies on renin will include experiments on synthesis and processing of both active and inactive renin and will parallel studies on the kidneys carried out by others. (3) Morphological studies employing immunocytochemistry to localize biologically active substances using immunofluorescence microscopy. Morphological studies will include intact membranes and isolated secretory granules. (4) Functional studies on secretory granules will parallel earlier studies from our laboratory on other secretory granules, including kidney renin granules, chromaffin granules, and neurosecretory granules. The long term goals include clarification of the endocrinology of the fetal membranes and improvement in diagnosis and/or management in various clinical conditions.